1. Week 4b: Ion channel structure
BIOL3833
Week 4b: Ion channel structure

2. Game plan for today: 12:00 to ~12:30 Lecture: Ion channel structure
12:30-1:15 Complete simulation experiments

5. Structural properties of ion channels:
Membrane spanning proteins that allow:
Selective permeability
Rapid ion movement
Gating (by voltage or ligands)
Inactivation mechanism (only some channels)
Modulation (fast/slow changes in voltage dependence or kinetics)

6. Proteins are made of these:

7. This is an ion channel:
Well, actually this is 1/4th of an ion channel

8. Voltage-gated K+ channel:
6 Transmembrane segments
1 Subunit
Pore region
4 subunits form channel
Need 20 AA to span membrane

9. Voltage-gated Na+ channel:
Four domains in ONE subunit
Pore region
IFM “inactivation loop”

10. Selectivity filter in the pore
Mystery:
K+ ions are larger than Na+ ions
Hydrated Na+ ions larger than hydrated K+ ions
How do sodium and potassium channels select?

11. Water is a polar molecule

14. Ion movement is way fast
How does the channel select for only one type of ion, while still allowing them to move at a rate approaching unrestricted free diffusion?

15. How? How can it be selective and fast? Rod MacKinnon figured it out:
Start Video at 15:15
End at 24:00

16. Béla

17. Choe (2002) Nat Rev Neurosci

18. S5 S6

19. Mechanism of voltage-gating

20. Mechanism of voltage-gating

21. Mechanism of inactivation

22. Modulation of channel function

23. Structural properties of ion channels produce:
Membrane spanning proteins that allow:
Selective permeability
Rapid ion movement
Gating (by voltage or ligands)
Inactivation mechanism (only some channels)
Modulation (function can be rapidly changed)

24. Ion channels are very finely tuned:
Small mutations cause disease states